Local immunopotentiation of the bladder in response to BCG immunotherapy

Abstract

Although intravesical Bacillus Calmette-Gu??rin (BCG) therapy for superficial bladder cancer is the most successful example of cancer immunotherapy, much remains unknown about its mechanisms of action.Using a standardized protocol for measuring urinary cytokines, we noted that BCG induces a mixed cytokine response, with a predominance of TH1 cytokines. Immune cells, bladder cancer cells and normal urothelium all produce cytokines and adhesion molecules, constitutively and on stimulation with BCG, both in vitro and in vivo. Booster instillations invoke a secondary immune response and persistent immunoactivation in responders but not in non-responders, suggesting that inappropriate dose and schedule may be tolerogenic.The addition of interferon alpha (IFNI?) to BCG induces more interferon gamma production, a cytokine known to increase the TH1 cellular immune response and anti-tumour efficacy. IFNI? with low dose BCG has significantly less toxicity and superior efficacy to standard dose BCG immunotherapy.